Thio-carbamyl-gamma-lactones



United States Patent 3,464,986 THIO-CARBAMYL-y-LACTONES Ranajit Ghoshand Nigel Douglas Bishop, Bracknell,

England, assignors to Imperial Chemical Industries Limited, London,England, a corporation of Great Britain No Drawing. Filed Feb. 10, 1966,Ser. No. 526,380 Claims priority, application Great Britain, Feb. 18,1965, 7,076/ 65 Int. Cl. C07d 87/46, /06; A01n 9/20 US. Cl. 260-2471 7Claims ABSTRACT OF THE DISCLOSURE Lactone-carbamyl compounds having theformula:

-R i l N---0--S 0 Y/ ll This invention relates to new carbamyl compoundsand to improved biologically active compositions containing the same.

According to the present invention there are provided newlactone-carbamyl compounds having the formula:

Y ll

wherein R stands for hydrogen or for a lower alkyl group and Z standsfor oxygen or sulphur and wherein X and Y, which may be the same ordifferent, each stand for a hydrogen atom or for an alkyl group ortogether represent a heterocyclic group including the adjacent N atom orwherein X stands for a hydrogen atom and Y stands for an allyl, aryl,halo-substituted aryl, aralkyl, heterocyclic, heterocyclic-alkyl,dialkylamino, alkoxy-carbonyl alkyl or lactone-carbamyl-alkyl group.

The group is referred to herein as a carbamyl acid residue. The lactonering is derived from tetrahydrofuran and contains 5 ring atoms. Thelactone ring may bear a substituent additional to the carbamyl acidresidue for example an alkyl group. The carbamyl acid residue which isrequired to be present is attached through a connecting atom of sulphurto the u-carbon atom of the lactone ring, that is to the carbon atomoccupying the position adjacent to the carbonyl group of the lactonering.

The nitrogen atom of the carbamyl acid residue may carry substituents Xand Y each of which may be an alkyl group especially one having from 1to 6 carbon atoms. When X stands for hydrogen the Y substituent may bean allyl; a dialkyl-amino group, or a substituted 3,464,986 PatentedSept. 2, 1969 ICC alkyl group, wherein the substituent may be an alkoxycarbonyl group, a phenyl group, a heterocyclic group or alactone-carbamyl group. The Y substituent may alternatively be a phenylgroup or a substituted phenyl group for example a halophenyl group, suchas chloro-phenyl group. A heterocyclic group, for example, a morpholinogroup, may also be attached to the nitrogen atom of the carbamyl acidresidue, or the latter may form part of a heterocyclic ring which cancontain one or more hetero atoms. Thus compounds are included whereinthe nitrogen atom forms part of a morpholine or piperidine ring.

Preferred compounds include those wherein R of the formula quoted abovestands for hydrogen or a methyl group, and Z stands for sulphur. When Zstands for oxygen it is preferred that R stands for a methyl group. Xand Y which may be the same or different, are prefery s-w 2 5-, 3 7-, 49, s 1s or nC H When X is H then Y may be for example C2H5 0 GHQ-3 0E3(CHM-CH The compounds of the invention may be obtained by a number ofdifferent processes. For example a salt of a carbamic acid may bebrought into reaction with a lactone having a replaceable halogen atomattached to a carbon atom of the lactone ring. Salts which may beemployed are alkali, alkaline earth and ammonium salts although salts oftertiary amines may also be used. For most purposes the sodium salts ofthe acids are generally employed. The halcrlactones which may beemployed may be either bromoor chloro-lactones. The halo-lactone isconveniently bromo-substituted, for example 2-oxo-3-bromo-tetrahydrofuran.

Carbamic acids and their salts vary greatly in their stability andmonothioand dithiocarbamic acids and their salts are especiallyunstable. Therefore in order to make monoand di-thiocarbamyl compounds2. salt of the respective acid is prepared preferably immediately beforeuse by bringing into reaction ammonia or a primary or secondary aminewith either carbonyl sulphide or carbon disulphide in the presence of abase. The amine used in the reaction should have attached to thenitrogen atom an aliphatic, aromatic or heterocyclic group.Alternatively the nitrogen atom should form part of a heterocyclic ring.If desired the salt may be separated from the reaction mixture beforetreatment with a halo-lactone, however compounds are also obtained veryconveniently by treating the reaction mixture of the carbonyl sulphideor the carbon disulphide, with the amine and the base, with thehalolactone. Both the formation of a carbamate salt and its subsequentreaction with the halo-lactone takes place readily at ambient orelevated temperatures i.e. below about C. and preferably below 50 C. Ingeneral both reactions are carried out preferably at a temperature offrom 20-40" C. The reactions may be carried out in the presence eitherof water or an organic liquid although for most purposes water providesa very satisfactory medium and may be added in the form of an aqueoussolution of the base used to form the carbamate salt or as a solution ofthe salt which is required to undergo reaction with the halo-lactone.

Other processes may be used for making the compounds including forexample the bringing into reaction in the presence of a base of acarbamyl halide, a thiocarbamyl halide, an isocyanate or anisothiocyanate with a hydroxyor mercapto-derivative of a lactone. Theprocesses are carried out preferably in the presence of a nonhydroxylicsolvent, for example diethyl ether, benzene or petroleum ether attemperatures of 100 C. and preferably at 20-40 C.

The compounds may be used both in agriculture and horticulture. Thecompounds display fungicidial activity and are especially useful for thecontrol of blast on rice (Piricularia oryzae), rust on wheat (Pucciniatriticiana) and sore skin on cotton (Rhizoctonia solani). The compoundsare also useful as intermediates in the preparation of otherbiologically active compounds.

The compounds are preferably converted into formulations to assist intheir application. For example they may be used in the form of a powderycomposition in which a minor amount of the compound is present inadmixture with a major amount of a solid diluent.

Suitable diluents include powdered kaolin, Fullers earth, gypsum, chalk,Hewitts earth and china clay. Since a certain number of the compoundsare liquid at ordinary temperatures they are usually applied moreconveniently in the form of a liquid preparation which is generally anaqueous dispersion or emulsion containing a surface active agent, forexample a wetting or dispersing agent. Suitable surface active agentsinclude condensation products of ethylene oxide with various substances,for example with alkylated phenols including octyl phenol and nonylphenol; sorbitan monolaurate; oleyl alcohol; cetyl alcohol; andpropylene oxide polymer. Other agents which are also suitable includecalcium dodecyl benzenesulphonate, calcium butyl naphthalenesulphonate,calcium lignosulphonate, sodium lignosulphonate, ammoniumlignosulphonate and glue. An alternative method for making liquidpreparations comprises dissolving the compounds in an organic solventfor example benzene, methanol, ethanol, or acetone, and then agitatingthe solution with water containing a surface active agent.

The compounds are conveniently made available by a supplier in the formof a concentrate which is a composition containing a high proportion ofthe compound and which therefore is generally required to be diluted,usually with water, before application. The concentrates may containfrom to 85% by weight of the compound although for practical purposesfrom 25-65% by weight is usually preferred. An especially satisfactoryform of concentrate comprises a concentrated solution of the compound inan organic solvent containing a surface active agent which is alsosoluble in the solvent. The diluted preparations which are suitable forapplication and which usually take the form of aqueous dispersions maycontain amounts of compound which can vary widely. However good resultsare generally obtainable by using from 0.025 to 0.2% by weight of thecompound. The compounds, preferably in a formulated condition, may beapplied by conventional methods. Thus compounds which are to be used fortheir capacity to control diseases caused by fungi to the foliage ofplants are applied more conveniently in the form of liquid preparationseither to the plants or the soil in which plants are to be grown or aregrowing. Solid compositions are however preferably for the treatment ofseeds to provide protection to the seeds from soil or seed bornediseases.

This invention is illustrated by the following examples:

Example 1 This example illustrates the preparation of 2-oxo-3(N-methyl-thiocarbamylthio)tetrahydrofuran having the formula:

A Solution of sodium hydroxide (8.0g) in water (15 cc.) was addeddropwise to a stirred mixture of methylamine (17.1 cc. of a 40% aqueoussolution) and carbon disulphide (12.6 cc.). The temperature of themixture during the addition was warmed to 40 C., and stirring wascontinued until all the carbon disulphide had reacted. The temperatureof the mixture was then reduced to 5 C. and 2-oxo-3-bromotetrahydrofuran (33.0 g.) was added dropwise, with vigorous stirring.After the addition had been completed the mixture was stirred for afurther period (0.5 hr.) and the product was then extracted with etherwhich was then removed by distillation.

As a result of the removal of the ether 2-oxo-3(N-methylthiocarbamylthio)tetrahydrofuran was obtained as an oil whichcrystallised on standing. The product was then purified byrecrystallisation from aqueous ethanol and was then found to possess amelting point of 60- 6l C.

Example 2 This example illustrates the preparation of 2-oxo-3 (N-allyl-thiocarbamylthio)tetrahydrofuran having the formula:

Carbon disulphide (6.3 cc.), was added dropwise with stirring to amixture of allylamine (7.5 cc.) and a solution of sodium hydroxide (4.0g.) in water (10 cc.). The temperature of the mixture was kept below 30C. until the reaction was completed. The mixture was then diluted withwater (15 cc.) and 2-oxo-3-bromo-tetrahydrofuran (16.5 g.) added slowlywith vigorous stirring. An oil was obtained which was extracted withether. The extract was then distilled to remove the ether and2-oxo-3(N-allylthiocarbamylthio)tetrahydrofuran was obtained as a liquidhaving a boiling point of 140 C. at a pressure of 0.1 mm. of mercury.

Example 3 This example illustrates the preparation of 2-oxo-3 (N- pchlorophenylthiocarbamylthio)tetrahydrofuran having the formula:

S I H o 01 NH 0 s A solution of p-chloro-aniline (12.8 g.) in ethanol(32 cc.) was added slowly to a mixture of carbon disulphide (7 cc.) andan aqueous solution of ammonia (Specific Gravity=0.880; 16 cc.) at 5 C.The mixture was stirred for 4 hours at 1520 C. and then cooled at 0 C. Ayellow precipitate of ammonium N-p-chlorophenyldithiocar bamate wasformed and was then removed by filtration and the resulting solid wasthen washed with alcohol (10 cc.). AmmoniumN-p-chlorophenyldithiocarbamate (16.2 g) formed in the above process wasdissolved in water (20 cc.) and the solution cooled to 5 C.2-oxo-3-bromotetrahydrofuran (12.1 g.) was then added slowly withvigorous stirring, and at the same time the temperature of the reactionmixture was maintained below 10 C. by external cooling.2-oXo-3(N-p-chlorophenylthiocarbamylthio)tetrahydrofuran was obtained asa White solid which on recrystallisation from ethanol was found to havea melting point of l06 C.

5 Example 4 This example illustrates the preparation of 2-oxo-3 (N-dimethylaminothiocarbamylthio)tetrahydrofuran having the formula:

The procedure of Example 2 was followed except that1,1-dimethylhydrazine (6 g.) was used in place of allyl-.

The procedure of Example 4 was followed except that1,1-di-isopropylhydrazine (11.6 g.) was used in place of 1,1dimethylhydrazine. 2-oxo-3(N-di-isopropylaminocarbamylthio)tetrahydrofuran, was obtained as ayellow solid which after recrystallisation from ethanol was found topossess a melting point of 123 C.

Example 6 This example illustrates the preparation of 2-oxo-3(N,N-dimethylthiocarbamylthio) tetrahydrofuran having the formula:

The procedure of Example 2 was followed except that a 30% aqueoussolution of dimethylamine (18 cc.) was used in the place of allylamine.2-oxo-3 (N,N-dimethylthiocarbamylthio) tetrahydrofuran was obtained as asolid which on recrystallisation from ethanol was found to possess amelting point of 120 C.

Example 7 This example illustrates the preparation of 2-oxo-3(N-methylthiocarbamylthio) methyltetrahydrofuran having the formula:

Carbon disulphide (6.3 cc.) was added dropwise to a 40% aqueous solutionof methylamine (16 cc.). The exothermic reaction yielded methylammoniumN-methyldithiocarbamate which was obtained as a dry salt by removalunder reduced pressure of the water and excess reactants. The dry salt(10 g.) was dissolved in water (20 cc.) and 2-oxo-3-bromo 5methyltetrahydrofuran (13 g.) was added dropwise with vigorous stirring.After stirring for a further period (2 hrs.) the product was extractedwith ether and the extract distilled to remove the solvent. 2-oxo-3(N-methylthiocarbamylthio)-5-methyltetrahydrofuran was obtained as anoil boiling at 132- 135 C. at a pressure of 0.2 mm. of mercury.

Example 8 This example illustrates the preparation of 2-oxo-3(N-ethylthiocarbamylthio) 5 methyltetrahydrofuran having the formula:

Carbon disulphide (6.3 cc.) was added carefully to a mixture ofethylamine (6.5 cc. of 70% aqueous solution) and ethylamine (10.1 cc.).The temperature of the mixture was maintained below 30 C. during theaddition. Stirring was continued until a homogeneous solution wasobtained which solidified on standing. The solid was then dissolved inwater (15 cc.) and 2-oxo-3-bromo-5-rnethyltetrahydrofuran was addeddropwise. During the addition the temperature of the reaction mixturewas maintained below 10 C. The addition was followed by a further periodof stirring (0.5 hr.)', after which the product was extracted with etherand theextract distilled to remove the solvent. 2-oxo-3(N-ethylthiocarbamylthio)-5-methyltetrahydrofuran was obtained as ayellow oil, boiling at a temperature of 123-131 C. at a pressure of 0.03mm. of mercury.

Example 9 This example illustrates the preparation of 2-oxo-3(N-isopropylthiocarbamylthio) 5 methyltetrahydrofuran having theformula:

This example illustrates the preparation of 2-oxo-3(N-n-butylthiocarbamylthio) 5 methyltetrahydrofuran having the formula:

CH3 t l The procedure of Example 8 was followed except that n-butylamine(10.5 cc.) was used in the place of ethylamine. 2-oxo-3(N-n-butylthiocarbamylthio) 5 methyltetrahydrofuran was obtained as ayellow oil boiling at a temperature of 136141 C. at a pressure of 0.1mm. of

mercury.

Example 11 The example illustrates the preparation of 2-oxo-3 (N nhexylthiocarbamylthio) 5 methyltetrahydrofuran having the formula:

I onxomnNH-b-s- 0 The procedure of Example 8 was followed except thatn-hexylamine (10.1 g.) was used in the place of ethylamine. 2-oxo-3(N-n-hexylthiocarbamylthio) 5 methyltetrahydrofuran was obtained as ayellow oil boiling at a temperature of 153-155 C. at a pressure of 0.05mm. of mercury.

7 Example 12 This example illustrates the preparation of 2-oxo-3 (N- ndodecylthiocarbamylthio) S-methyltetrahydrofuran having the formula:

allylthiocarbamylthio) S-methyltetrahydrofuran having the formula:

The procedure of Example 2 was followed except that2-oxo-3-bromo-5-methyltetrahydrofuran (17.9 g.) was used in the place of2-oxo-3-bromo-tetrahydrofuran. 2-

oxo-3 (N-allylthiocarbamylthio)-5-methyltetrahydrofuran was obtained asan oil boiling at a temperature of 142 144 C. at a pressure of 0.07 mm.of mercury.

Example 14 This example illustrates the preparation of 2-oxo-3 (N-phenylthiocarbamylthio) S-methyltetrahydrofuran having the formula:

The procedure of Example 8 was followed except that aniline (9.3 cc.)was used in the place of ethylamine. 2-0xo-3 (N-phenylthiocarbamylthio)S-methyltetrahydrofuran was obtained as a solid which onrecrystallisation from ethanol was found to melt at 119 C.

Example 15 This example illustrates the preparation of 2-oxo-3 (N- pchlorophenylthiocarbamylthio) S-methyltetrahydrofuran having theformula:

The procedure of Example 3 was followed except that 2 oxo-3-brorno-5methyltetrahydrofuran (12.8 g.) was used in place of2-oxo-3-br0mo-tetrahydrofuran. 2-oxo-3 (Np-chlorophenylthiocarbamylthio) S-methyltetrahydrofuran was obtained asa solid which after purification by recrystallisation from a mixture ofchloroform and 40-60 petroleum ether was found to melt at a temperatureof 110-112 C.

8 Example 16 This example illustrates the preparation of 2-oxo-3 (N-dimethylaminothiocarbamylthio) 5 methyltetrahydrofuran having theformula:

The procedure of Example 4 was followed except that 2 0x0-3bromo-S-methyltetrahydrofuran (17.8 g.) was used in the place of2-oxo-3-bromo-tetrahydrofuran. 2- oxo-3 (Ndimethylaminothiocarbamylthio) S-methyltetrahydrofuran was obtained as asolid which on recrystallisation from ethanol was found to posses amelting point of -127 C.

Example 17 This example illustrates the preparation of 2-oxo-3 (N-benzylthiocarbamylthio) 5 methyltetrahydrofuran having the formula:

The procedure of Example 8 was followed except that benzylamine (10.7g.) was used in the place of ethylamine. 2-oxo-3(N-benzylthiocarbamylthio) 5 methyltetrahydrofuran was formed as a solidwhich on recrystallisation was found to possess a melting point of 89 C.

Example 18 This example illustrates the preparation of 2-oxo-3(N-l-phenethylthiocarbamylthio) 5 methyltetrahydrofuran having theformula:

CH3 S The procedure of Example 8 was followed except thatl-phenethylamine (12.1 g.) was used in the place of ethylamine. 2-oxo-3(N-1-phenethylthiocarbamylthio)-5- methyltetrahydrofuran was obtained asa solid which after recrystallisation from ethanol was found to possessa melting point of 98 C.

Example 19 This example illustrates the preparation of 2-oxo-3 (N- 2phenethylthiocarbamylthio)-S-methyltetrahydrofuran having the formula:

The procedure of Example 8 was followed except that Z-phenethylamine12.1 g.) was used in the place of ethylamine. 2-oxo-3(N-Z-phenethylthiocarbamylthio)-5-methyltetrahydrofuran was obtained asa solid which after recrystallisation from ethanol was found to possessa melting point of 102 C.

Example 20 This example illustrates the preparation of 2-ox0-3 (Ntetrahydropyran 2 ylmethylthiocarbamylthio)-5- methyltetrahydrofuranhaving the formula:

'9 The procedure of Example 8 was followed, except that2-aminomethyltetrahydropyran (11.5 g.) was used in the place ofethylamine. The compound was obtained as a viscous yellow oil having aboiling point of 158-168 C. at a pressure of 0.15 mm. of mercury.

Example 21 This example illustrates the preparations of 2-oxo-3(N-ethoxycarbonylmethylthiocarbamylthio) 5 methyltetrahydrofuran havingthe formula:

Example 22 This example illustrates the preparation of 2-oxo-3(N,N-dimethylthiocarbamylthio) 5 methyltetrahydrofuran having theformula:

CH3- SI The procedure of Example 6 was followed except that2-oxo-3-bromo-5-methyltetrahydrofuran (17.8 g.) was used in the place of2-0xo-3-bromo-tetrahydrofuran. 2- oxo-3 (N,Ndimethylthiocar'bamylthio)-5-methyltetrahydrofuran was obtained as asolid which after recrystallisation from ethanol was found to possessmelting point of 84 C. v "Example 23.

This example illustrates the preparation of 2-oxo-3(N-methylcarbamylthio)-5-methyltetrahydrofuran having the-formula:

Carbonyl sulphide (11.8 g.) was bubbled into a stirred ice-cooledmixture of a 40% aqueous solution of methylamine (15.2 cc.),triethylamine (20.2 g.) and water (50 mls.) at a rate of 1 to 2 litresper hour. When the addition was completed,-the mixture was treated with2-oxo-3-bromo-5 methyltetrahydrofuran (35.8 g.-), dropwise, withvigorous stirring. The mixture was then allowed to stand overnight afterwhichsodium chloride was added. The aqueous solution was then extractedwith ether after which the extract was distilled to remove the ether.2-oxo-3 (N- methylcarbamylthio)-5-methyltetrahydrofuran was 1 obtainedas a solid which after recrystallisation from diethyl ether was found topossess a melting point of 88 C.

' Example 24 This example illustrates the preparation of 2 oxo-3(N-ethylcambamylthio)-5 methyltetrahydrofuran having the formula:

The procedure of Example 23 was followed, except that ethylamine (70%aqueous solution, 13 cc.) was used in the place of the methylaminesolution. 2-oxo-3 (N-ethylcarbamylthio)-5-methyltetrahydrofuran wasobtained as a yellow oil having a boiling point of 134138 C. at apressure of 0.15 mm. of mercury.

Example 25 This example illustrates the preparation of 2-oxo-3(N-isopropylcarbamylthio) tetrahydrofuran having the formula:

The procedure of Example 23 was followed except that isopropylamine(11.8 g.) was used in the place of the methylamine solution, and2-oxo-3-bromo-tetrahydrofuran (33 g.) was used in the place of the2-oxo-3-bromo-5- methyltetrahydrofuran. 2-oxo-3(N-isopropylcarbamylthio) tetrahydrofuran was obtained as a solid whichon recrystallisation from ethanol was found to possess a melting pointof 132 C.

Example 26 This example illustrates the preparation of 2-oxo-3(N-dimethylaminocarbamylthio) 5 methyltetrahydrofuran having theformula:

The procedure of Example 23 was followed except that1,1-dimethylhydrazine (12 g.) was used in the place of the methylaminesolution. 2-oxo-3 (N-dimethylaminocarbamylthio)-5-methyltetrahydrofuranwas obtained as a White solid, which after recrystallisation from waterwas found to possess a melting point of 129 C.

Example 27 This example illustrates the preparation of ethylene bis(2-0xo-S-methyltetrahydrofuran-3-yldithiocarbamate) having the formula:

ti ll Carbon disulphide (6.3 cc.) was added dropwise to a mixture ofethylene diamine (3 g.), triethylamine (10.1 cc.), ethanol (20 cc.), andwater (25 cc.), with stirring and external cooling. After the reactionwas completed, 2-oxo-3-bromo-5-methyltetrahydrofuran (17.8 g.) was addeddropwise with vigorous stirring. Ethylene bis (2-oxo-S-methyltetrahydrofuran 3-yldithiocarbamate) was obtained initiallyas a yellow oil which solidified on standing at 0 C. The product wasrecrystallised from alcohol and was then found to possess a meltingpoint of C.

1. 1 Example 28 This example illustrates the preparation of 2-oxo-3(thiocarbamylthio)-5-methyltetrahydrofuran having the formula:

To a solution of ammonia in ethanol (11.4% w./v.; 250 cc.) was addedwith stirring a solution of carbon disulphide (60 cc.) in ethanol (250cc.), the temperature being kept at 20 C. during the addition. Themixture was stirred at 20 C. for two hours, followed by a period ofstanding (16 hours), after which the yellow crystalline precipitate ofammonium dithiocarbamate was filtered off.

To a solution of ammonium dithiocarbamate (12 g.) in water cc.) wasadded with stirring 2-oxo-3-br0mo- 5-methyltetrahydrofuran (17.9 g.)dropwise with external cooling to keep the reaction temperature below 25C. when a yellow oil was separated which solidified on standing. Onrecrystallisation from chloroform this yielded 2-oxo-3(thiocarbamylthio)-5-methyltetrahydrofuran as a cream solid having amelting point of 110 C.

Example 29 This example illustrates the preparation of 2-oxo-3(N-pentamethylene thiocarbamylthio) tetrahydrofuran having the formula:

Example 30 This example illustrates the preparation of 2-oxo-3(N-pentamethylenethiocarbamylthio) 5 methyltetrahydrofuran having theformula:

The procedure of Example 29 was followed except that2-oxo-3-bromo-5-methyltetrahydrofuran (17.9 g.) was used in the place of2-oxo-3-bromo-tetrahydrofuran 2- 0x0 3(N-pentamethylenethiocarbamylthio)-5-methyltetrahydrofuran is a solidhaving a melting point of 78 C. after recrystallisation from ethanol.

Example 31 This example illustrates the preparation of 2-oxo-3 (N-3-oxapentamethylenethiocarbamylthio) tetrahydrofuran having the formula:

The procedure of Example 29 was used except that morpholine (8.7 cc.)was used in the place of piperidine.

The product 2-oxo-3 (N-3-oxa-pentamethylenethiocarbamylthio)tetrahydrofuran is a solid having a melting point of 71 C. afterrecrystallisation from ethanol.

Example 32 This example illustrates the preparation of 2-oxo-3 (N3-oxa-pentamethylenethiocarbamylthio)-5-methyltetrahydrofuran having theformula:

The procedure of Example 30 was followed except that morpholine (8.7cc.) was used in place of piperidine. The product 2 oxo-3(N-3-oxa-pentamethylenethiocarbamylthio)-5-methyltetrahydrofuran is asolid having a melting point of 114 C. after recrystallisation fromethanol.

Example 33 This example illustrates the preparation of 2-oxo-3(thiocarbamylthio) tetrahydrofuran having the formula:

This example illustrates the preparation of 2-oxo-3(N-hexamethylenethiocarbamylthio) 5 methyltetrahydrofuran having theformula:

The procedure of Example 30 was followed except that hexamethyleneimine(9.9 g.) was used in place of piperidine. The product 2-oxo-3(N-hexamethylenethiocarbamylthio)-5-methyltetrahydrofuran is a solidhaving a melting point of 60 C. after recrystallisation from ethanol.

Example 35 This example illustrates the preparation of 2-oxo-3(N-pentamethylenecarbamylthio) 5 methyltetrahydrofuran having theformula:

The procedure of Example 23 was followed except that piperidine (18.6g.) was used in place of the methylamine solution. The product, 2-ox0-3(N-pentamethylenecarbamylthio)-5-methyltetrahydrofuran, was obtained asan oil having a boiling point of 146-150 C. at a pressure of 0.03 mm. ofmercury.

13 Example 36 This example illustrates the preparation of 2-oxo-3(N-phenylcarbamylthio)--methyltetrahydrofuran having the formula:

14 (N-4-morpholinylthiocarbamylthio) tetrahydrofuran, a white solidhaving a melting point of 173-174 C.

Example 38 This example illustrates the preparation of 2-oxo-3 5(N-Z-phenethylcarbamylthio) tetrahydrofuran having the 0 .-OH3 formula:

A I, -om-om-uuzis O The procedure of Example 26 was followed except Nthat aniline (18.6 g.) was used in the place of 1,1-d1- 0methylhydrazine. The product, 2-oxo-3(N-phenylcarbamylthio)-5-methyltetrahydrofuran is a solid having amelting point of 125 C. after recrystallisation from a mixture Theprocedure of Example 23 was followed except of chloroform and Petroleumether (m-60 that Z-phenethylamine was used in the place of the methyl-Example 37 amine solution and 2-oxo-3-bromo-tetrahydrofuran was used inplace of the 2-oxo-3-bromo-S-methyltetrahydro- This example illustratesthe preparation of 2-oxo-3 furan. 2-oxo-3 (N-2-phenethylcarbamylthio)tetrahydro- (N-4-morpholinylthiocarbamylthio) tetrahydrofuran havfuranis an oil having a boiling point of 174 C. at a presing the formula:sure of 0.04 mm. of mercury.

The compounds were tested against various fungal 25 diseases and theresults of these tests are shown in Tables I 1 and 2 below. NH 0 In thetests involving foliage diseases the plants were 0 sprayed with asolution or suspension containing 500 ll parts per million of the activecompound and 0.1% of a Wetting agent and after 24 hours were inoculatedwith the disease the extent of which was assessed visually at A Solutlonof f hydroxlfje (7 Water (10 the end of the test. The results are shownin Table 1 cc.) was added dropwlse to a stirred m1xture of carbon belowas grading giving the percentage amount of disulphide (5.25 cc.) andN-amlnomorpholme hydrodisease as follows. chloride (12.1 g.) in water(40 cc.), followed by stlrnng 5 the mixture at 40 C. for 2 hours. Tothis mixture is Grading: Percentage amount of disease added2-oxo-3-brom0-tetrahydr0furan (14.1 g.) dropwise 0 61 to 100 withstirring, followed by warming for 1 hour at 40 C. 1 26 to After coolingto 5 C., the precipitate was collected by 2 61 25 filtration andrecrystallised from ethanol to yield 2-oxo-3 40 3 5 TABLE 1 ErysiphePhytophthora Puccim'a Plasmopam Piricularz'a cz'chomcearum infestansrecondita vz'tz'cola oryzae Powdery Late Downy mildew blight Rust mildewBlast Cucumber Tomato Wheat Vine Rice Duration of Test in days ExampleNo.:

In the tests involving seed and soil, for the diseases Fusarium culmorumand Pythium ultimum the seeds were dressed with a formulation containing25% of the active ingredient and 75% china clay to give on the seed1,000 ppm. (wheat) and 500 p.p.m. (peas). The seeds were then sown in apartially sterilized soil to which a 2% inoculum of the fungus had beenadded. The seedlings were examined at the end of the test and thefigures given in Table 2 are the number of healthy plants expressed as apercentage. In the test against Rhizoctonia solani the active compoundwas mixed at the rate of 150' parts per million with soil which had beenartificially inoculated with a pure culture of the disease. Untreatedcotton seed was sown in the soil in pots 3 days later and a count of thehealthy seedlings was made at the end of the test. The figures in Table2 are expressed as a percentage of the seedlings which were healthy. Inthe test against Xanthomonas malvacearum naturally infected cotton seedwas dressed at the rate of 1250 parts per million of the active.compound and the seed was then sown in sterilized loam in pots. At theend of the test the disease was assessed and the figures given in thetable are the number of healthy plants expressed as a percentage.

TABLE 2 Fusarium Pythium Rhizoctonia Xanthomonas culmorum ultimum salamimalvacezzrum (Foot-rot) (Foot-rot) (Soreshiu) (Black arm) Wheat PeasCotton Cotton Example No. 20 days 20 days 20 days 10 days What we claimis: 1. A lactone carbamyl compound having the formula:

wherein R stands for hydrogen or lower alkyl, Z stands 50 for oxygen orsulfur, X and Y each stand for hydrogen,

or alkyl of up to 12 carbon atoms or together with the adjacent nitrogenatom represent a hexamethylenimino, morpholino, or piperidino ring orwherein x stands for a hydrogen atom and Y stands for allyl,chlorophenyl, phenyl-substituted alkyl containing 1 to 2 carbon atoms,phenyl, morpholino, dialkylamino containing up to 3 carbon atoms in eachalkyl group, ethoxycarbamylrnethyl, tetrahydropyran-2-yl-methyl, ..or5e'meth'yl-2-oxo-3-thiocurbamylthio-tetrahyd'rofuran-ethylene, R. beingalkyl when Y is alkyl.

2. A lactone carbamyl compound as claimed in claim 1 in which Z standsfor sulphur and R and Y each stand for a methyl group to give thecompound 2-oxo-3 (N- methylthio ca rbamylthio -5 -methy1tetrahydrofuran.

3. A lactone carbamyl compoundwas claimed in claim 1 in which R standsfor hydrogen or a methyl group, X stands for hydrogen and Y stands for adimethyl amino or di-isopropylamino group.

4. A lactone carbamyl compound 'as claimed in claim 1 in which R standsfor hydrogen or a methyl group, Z stands for sulphur, X stands forhydrogen and Y stands for an allyl radical.

5. A lactone carbamyl compound as claimed in claim 1 in which X standsfor hydrogen and Y stands for a phenyl, chlorophenyl, benzyl or forphenethyl.

6. A lactone carbamyl compound as claimed in claim 1 in 'Which X and Ytogether with the adjacent nitrogen 'atom constitute a morpholino or'piperidino group, or in which X stands for hydrogen and Y stands for amorpholino group.

7. A lactone carbamyl compound as claimed in claim 1 in which Z standsfor sulphur, R stands for a methyl group, X stands for hydrogen and Ystands for a tetrahydropyran-Z-yl methyl group, anethoxy-carbonyl-methyl group or a S-methyl substituted2-oxo-3-thiocarbamylthiotetrahydrofuran ethylene group.

References Cited FOREIGN PATENTS 940,536 10/1963 Great Britain.

OTHER REFERENCES German Pat. No. 801,992, abstracted in Chem. Abs. 5179,June 1951.

HENRY R. JILES, Primary Examiner C. M. SHURKO, Assistant Examiner US.Cl. X.R.

ewe-w.

333 STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,464,986Dated September 2, 1969 Invencofls) Ranajit Ghosh and Nigel DouglasBishop It is certified that error appears in the above-identified patentand that said Letters Patent: are hereby corrected as shown below:

Claim 1, line 11 (Column 16, line 7) of .the patent"ethoxycarbamylmethyl" should read -ethoxycarbonylmethyl- In theAbstract, line 11 (Column 1, line 28) of the patent) "Piricularia"should read -Piricutaria- Signed and sealed this 11th day of January1972.

(SEAL) Attest':

EDWARD MELBTCHERQJR. ROBERT GOTTSCI-LALK Attesting Officer ActingCommissioner of Patents

